The introduction of inhalation combination products has led to significant advancements in the treatment of respiratory and pulmonary diseases and disorders. There is considerable interest in the development of the next generation of therapies with the aim of improved safety profiles and enhanced patient outcomes. One approach is to develop therapies incorporating additional therapeutic agents, for example more than one bronchodilator and an anti-inflammatory agent.
The development of inhalation combination products raises the significant pharmaceutical challenge of maintaining a controllable ratio of drug components during various stages of drug formulation and drug delivery. This challenge is especially acute with regards to the development of combination therapies involving three or more active pharmaceutical agents.
There is therefore a need to develop new pharmaceutical compositions, comprising three or more active agents, which enable the controlled delivery of active agents to the lung.
US2009/0298802 (Schering-Plough Corporation) discloses inhalable medicaments and methods based on an anti-cholinergic in combination with a corticosteroid, and a long acting beta agonist, for simultaneous or sequential administration.
WO2010/138884 (Pearl Therapeutics) provides compositions, methods and systems for pulmonary or nasal delivery of two or more active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium. Example 9 describes a composition including glycopyrrolate particles, formoterol fumarate particles, mometasone furoate particles and suspending particles in HFA 134a propellant. Example 10 describes compositions including glycopyrrolate or tiotropium bromide, in combination with formoterol fumarate and mometasone furoate.
WO2012/110770 (Cipla Limited) claims pharmaceutical compositions for inhalation comprising glycopyyrolate, a beta2-agonist, and optionally an inhaled corticosteroid.